The objective of this research is to characterize the molecular structure and stabilizing interactions of the myelin sheath. The structural neuropathology of myelin will be studied by coordinated X-ray and neutron diffraction, thin-section and freeze-fracture electron microscopy, and chemical analysis. Measurements will be made on intact myelin and on purified myelin membranes isolated from the central and peripheral nervous systems. Analysis of myelin in normal and pathological tissue, in neurological mutants, and in animals with induced demyelination will yield information on the protein and lipid interactions which stabilize the membrane array. The heterogeneity of the myelin lattice will be analyzed by electron microscopy using comparative diffraction methods to correlate the structure seen in micrographs to that in the intact tissue. Selective removal or modification of molecular components from myelin should establish the location of these components, and may indicate which molecular species are essential for sheath integrity. This combined structural-chemical approach will help to elucidate the molecular processes involved in demyelinating diseases such as multiple sclerosis.